Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04457505 |
| Other study ID # |
CIBERESUCICOVID |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 8, 2020 |
| Est. completion date |
December 31, 2021 |
Study information
| Verified date |
July 2022 |
| Source |
Consorcio Centro de Investigación Biomédica en Red, M.P. |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
The latest epidemiological data published from Chine reports that up to 30% of
hospital-admitted patients required admission to intensive care units (ICU). The cause for
ICU admission for most patients is very severe respiratory failure; 80% of the patients
present with severe acute respiratory distress syndrome (SARS) that requires protective
mechanical ventilation.
Five percent of patients with SARS require extracorporeal circulation (ECMO) techniques.
Global mortality data has been thus far reported in different individual publications from
China. Without accounting for those patients still admitted to hospital, bona fide
information (from a hospital in Wuhan) received by the PI of this project estimates that
mortality of hospitalized patients is more than 10%. Evidently, mortality is concentrated in
patients admitted to the ICU and those patients who require mechanical ventilation and
present with SARS. As data in China was globally reported, risk factors and prognosis of
patients with and without SARS who require mechanical ventilation are not definitively known.
The efficacy of different treatments administered empirically or based on small, observation
studies is also not known. With many still admitted at the time of publication, a recent
study in JAMA about 1500 patients admitted to the ICU in the region of Lombardy (Italy)
reported a crude mortality rate of 25%. The data published until the current date is merely
observational, prospective or retrospective. Data has not been recorded by analysis performed
with artificial intelligence (machine learning) in order to report much more personalized
results. Furthermore, as it concerns patients admitted to the ICU who survive, respiratory
and cardiovascular consequences, as well as quality of living are completely unknown.
The study further aims to investigate quality of life and different respiratory and
cardiovascular outcomes at 6 months, as well as crude mortality within 1 year after discharge
of patients with COVID-19 who survive following ICU admission. Lastly, with the objective to
help personalize treatment in accordance with altered biological pathways in each patient,
two types of studies will be performed: 1) epigenetics and 2) predictive enrichment of
biomarkers in plasma.
Hypothesis
- A significant percentage of patients (20%) admitted to the hospital with COVID-19
infection is expected to require ICU admission, and need mechanical ventilation (80%)
and, in a minor percentage (5%), ECMO.
- Patients who survive an acute episode during ICU hospitalization will have a yearly
accumulated mortality of 40%. Those who then survive will have respiratory consequences,
cardiovascular complications and poor quality of life (6 months).
Description:
Objective and Purpose of Study
1. The main objective is to determine risks factors and prognosis of patients with COVID-19
infection who have been admitted to Spanish ICUs between the beginning and end of the
pandemic in Spain. Special attention will be placed on identifying differential
expression of prognostic factors based on sex.
2. The second objective is to perform a follow-up of patients within 6 months after
discharge from ICU and hospital in order to determine mortality (including at 1-year
mark), functional respiratory and cardiovascular consequences, and quality of life.
3. The third objective is to perform an epigenetic study in cases, in which a blood sample
can be drawn. The aim of such undertaking is to define molecular signatures in liquid
biopsies that can provide information regarding prognosis, and treatment monitoring and
response to therapy.
4. Lastly, predictive ability of response to therapy and mortality will be assessed from a
panel of protein biomarkers that participate in key physiological pathways of the
disease's pathogenesis. This could, in turn, help select prospective treatments with
greater potential of being successful in each patient.
Principal and Secondary Variables
1. Prior epidemiological data of the patient
2. Biological and clinical data, including treatment administered upon hospital admission
3. Biological and clinical data, including treatments administered upon and during ICU
admission until either discharge from ICU or hospital, or death
4. Specific data regarding artificial ventilation and ECMO since the beginning, as well as
sequentially, from intubation to either extubation or death
5. Biological and clinical data upon hospital discharge
6. Clinical follow-up of patients who survive within 6 months, including: functional
respiratory tests, echocardiograms and surveys regarding quality of life
7. Intrahospital and intra-ICU mortality will be registered at 28- and 90-day marks, as
well as within 6 months and 1 year
8. 1000 blood samples will be drawn for the epigenetic study The molecular profile of a
non-coding RNA (ncRNA), specifically the microRNA (miRNA) pattern in liquid biopsy, will
be analyzed. A circulating miRNA signature is closer to the phenotype than genomic
markers and can provide information regarding epigenetic regulation, cell activation,
tissue repair, and metabolic processes in addition to that afforded by clinical
predictors and classic risk factors. miRNAs offer appropriate biochemical properties
that are highly stable; have a long half-life in biological samples used in clinical
laboratories (serum/plasma); can be efficiently and relatively rapidly quantified with
high sensitivity and specificity by RT-qPCR; and can serve as a profitable tool for the
assessment of risks and disease control.
All of these characteristics have led distinct authors to propose the clinical application of
miRNA in either the short or medium term.
The experimental design comprises two phases. In the first approximation, a screening of
non-coding RNA (ncRNA) will be performed in a sub-population of patients (n=200). The number
of samples surpasses the quantity recommended for this type of studies. (Schurch y cols.,
RNA, 2016). A quotation will be requested for the screening of ncRNA by HTG EdgeSeq miRNA
Whole Transcriptome Assay system (HTG). Using next generation sequencing (NGS), this method
allows for the quantification of 2083 human candidates. All of the procedure steps will be
completed in suitable physical locations in accordance with code OP No. 0028. All of the
samples will be prepared in accordance with code No. 0036.
Screening results will be validated in the validation cohort (n=800) with RT-qPCR, a
gold-standard technique. The budget includes material necessary for RNA extraction (miRNeasy
Serum/Plasma isolation kits, Qiagen; spike-in; carrier RNA; consumables) and expression
quantification of ncRNA in biofluids (RT-qPCR miRCURY LNA Universal RT microRNA PCR System
kits, Qiagen; endogenous controls; consumables. Studies will be carried out at the TRRM Group
facilities in the IRBLleida. The laboratory has the necessary team and material to isolate
and quantify RNA, and store reagents and samples (cold stores, freezers of 20ºC and -80ºC).
9.- For the study of prognostic biomarkers, concentration of biomarkers in plasma that are
key to potentially useful drugs' mechanism of action in this disease will be assessed. This
quantification could provide guidance on drug usage (lymphocyte count will be obtained from a
blood count):
